Intercellular signaling 1. Contact-dependent - membrane-membrane contact 2. Paracrine - signals released and recognized by neighboring cells 3.

Synaptic - neurotransmitters at synapses 4. Endocrine - hormone travel through bloodstream Relay signals Intracellular signaling molecules small intracellular mediators: - relay - amplify - integrate - spread - anchor - modulate *Squid can escape predators by activating bacteria in them that glow. Bacteria need quorum sensing to glow. Cell surface receptor proteins Ion channel coupled - transmitter-gated - ionotrophic receptors G-protein coupled receptor - receptor binds to go-protein and assoc. enzymes G-proteins - guanine nucleotide-binding proteins, family of GTPases involved in second messenger cascades Signal tranduction via G-proteins 1. G-proteins (GTPase) activate other enzymes 2. Other enzymes (adenylate cyclase) catalyze formation of cAMP from ATP 3. cAMP serves as relay signal 4. PKA (cAMP dependent protein kinase) is activated 5. PKA helps activate CREBP (cAMP response element binding protein) cAMP - ATP -> cAMP - catalyzed by adenylate cyclase G protein and inositol phospholipid signaling pathway - G protien activates PhosphoLipase C - PLCB cleaves phosphatidyl inositol 4,5 bisphosphate - PI(4,5)P2 --> IP3 + diacylglycerol IP3 - small intracellular mediator - Goes to ER and opens IP3-gated Ca-release channels (IP3 receptors) Diacylglycerol - can be cleaved from the synthesis of eicosanoids (prostaglandins) activates PKC (protein kinase C) Enzyme coupled-receptors 5.Receptor Tyr Kinase (RTK) Properties of RTKs

-Phosphorylate themselves does not need external stimuli, once activated (bad side) docking sites for intracellular signaling proteins dimerization activates normal RTKs Proteins with SRC homology domains (SH) bind to phosphorylated Tyr for inc or dec of signals. Intracellular proteins that bind RTKs: - PI-3 Kinase - Phospholipase C - Monomeric GTPases (e.g. Ras) - usually signal proteins are the growth factors Ras (GTPase) relays signal from cell-surface receptor important because 30% of human tumors have Ras mutants Ras and RTK is sometimes mediated by adaptors with SH domains Mitogen activated protein kinase (MAPK) module binds to Ras - MAPK module cascade components: - Raf (MAP kinase^3) - Mek (MAP kinase^2) - Erk (MAP kinase) 6.involved in G1 cyclin gene activation 7.prevents cross-talk scaffold proteins bind MAPK molecules 8.can cause transient changes in protein activity or changes in gene expression *growth factors can stimulate stem cells. *some mutations can release different kinds of integrins that release the cancer cells from the tissue - TH (Helper T-cells) - signals body when infected by viruses - macrophages engulf and transform into antigen presenting cells (APC) - APC allow TH to bind and activated to form cytokine, interleukin, Tc (cytotoxic), and activate B cells (make antibodies). Signal Transduction in Bacterial Chemotaxis - histidine-kinase associated receptors Signal Transduction in Plants - Ser/Thr kinases - largest class of cell-surface receptors - contain leucine-rich repeats (LRR) - LRR receptor kinases - majority of plant surface receptors Neurons and Electrical Properties of Membranes Neuron: Body ---> axon ---> terminal branches -receive, conduct, transmit Signal propagation 6.electrical disturbance spreads to other parts 7.gets weaker as distance increases 8.can be amplified

Membrane Potential voltage difference across a membrane due to excess ions on each side Na channel - closed or open - inactivated membrane is refractory to stimulation - Na abundant outside cell (polarized membrane) - With stimuli, channel opens and floods cell with Na (depolarized membrane) - after some time, channel will be inactivated *channels are activated by ATP, ligands, or voltage Action potential/nerve impulse rapid, transient, self-propagating electrical excitation triggered by pulse partially depolarizes membrane in absence of Na+ channel, membrane potential relax to resting state. due to efflux of K+ via voltage-gated K+ channels course of opening and subsequent inactivation of voltage gated Na channel membrane cannot fire a second action potential until Na+ channel is back at resting state. Voltage-gated Cation Channels - generates action potentials - Triggered by depolarization of membrane - shift to less negative value inside (not necessarily positive right away) - In nerve and skeletal muscle -> Voltage-gated Na+ channels allow small amount of Na+ down its electrochemical gradient -> positive feedback Transmitter-gated Ion Channels - Synapse-specialized - Cells are electrically isolated - Presynaptic cell - Synaptic cleft - Postsynaptic cell - Nurotransmitters - signal molecules degraded by enzymes taken up by glial cells - Converts extracellular signal to electrical - Insensitive to membrane potential - Chemical synapse more versatile that electrical synapse (gap junctions) which are used by neurons - Cannot produce self-amplifying excitation - Highly selective binding sites Type of Neurotransmitters 9. Excitatory - influx of Na+ 10.Inhibitory - influx of K+ or ClCl- channels buffers membrane potential - Faster than G-protein and enzyme coupled receptors Neuromuscular Transmission - Nerve impulses arrive at junction and open Ca channel for uptake

- Acetylcholine bind receptors at muscle cell - Na+ ions flood muscle cell Major targets of psychoactive drugs - Curare - treats insomnia, anxiety, depression, schizophrenia - Valium, Librium - tranquilizers bind GABA receptors, inhibits GABA Lower concentrations to open Cl channels - Prozac - antidepressant Acetylcholine Receptor - First ion channel to be cloned - Abundant in electric eels